The project will utilize a combined biochemical and genetics approach in the study of murine Ia antigens, with the goal of understanding how these membrane glycoproteins might function in the regulation of immune responses. Two-dimensional polyacrylamide gel electrophoresis and peptide mapping of immunoprecipitated Ia antigens will be used to examine the polypeptide chain composition and polymorphism of Ia antigens. In particular, the significance of the invariant Ia-associated chain (Ii) will be studied, as will be the formation of mixed-haplotype Ia dimers in heterozygotes. Variant mouse lymphoid cell lines with missing or abnormal Ia antigens will be obtained through immunoselection procedures and analyzed for the basis for their defects. Such variants should provide information on the genetics, structure, and biosynthesis of Ia antigens.